Abstract Objectives: To evaluate the efficacy of minimizing Stereotactic Body Radiation Therapy (SBRT) effects on lymphocytes and improving overall survival and immune function by selectively reducing dose to blood rich organs, and increasing the dose confomality in the thorax. Method: This will be achieved in two steps: (A) Determine lymphocyte depletion, phenotype and function of lymphocytes in optimized versus un-optimized plans in total of 50 patients under a randomized pilot study. We will evaluate peripheral blood mononuclear cells collected at baseline and at end of treatment, 4, and 24 weeks after lung SBRT on the clinical trial and compare the data for the two arms. (B) Improve the existing simulation algorithm to predict the total lymphocyte loss for a given Radiation Therapy (RT) beam plan using the clinical trial data. This model will take into account patient specific (i) total blood volume (ii) initial lymphocyte count (iii) tumor volume (iv) the organs from the Thorax CT data set (v) time dependent dose map through each organ for a given delivery system, and plan, and convolve these with general information from published literature such as (i) varying blood output to organs (ii) blood velocity for all organs (iii) Random mixing of blood after each trip through the exposed dose area, with the remaining blood volume of the body.